PLGA microspheres for improved antigen delivery to dendritic cells as cellular vaccines

Abstract

Dendritic cells (DC) are currently employed as cellular vaccines in clinical trials of tumor immunotherapy. In most trials, peptide epitopes derived from tumor antigens are being exogenously loaded onto human DC for binding to MHC class I molecules. While this is a convenient method, it suffers from the drawback that the persistence of class I/peptide complexes on the cell surface is in the order of a few hours. This drawback limits the success of vaccination. We have investigated biodegradable poly(d,l-lactide-co-glycolide) microspheres (PLGA-MS) as delivery tools for antigen loading of human monocyte-derived DC (hMoDC). Immature hMoDC readily take up PLGA-MS and present epitopes from encapsulated proteins or peptides both on MHC class I and class II. Interestingly, antigen presentation by hMoDC was markedly prolonged when hMoDC were charged with PLGA-MS-encapsulated as opposed to soluble antigens. The properties of hMoDC with respect to migration, cytokine secretion, survival and allostimulation were not adversely affected by the uptake of PLGA-MS. In this article, we will review the properties of PLGA-MS as an adjuvant and summarize recent data on their potential for antigen delivery to dendritic cells.

Hollow microneedle-mediated intradermal delivery of model vaccine antigen-loaded PLGA nanoparticles elicits protective T cell-mediated immunity to an intracellular bacterium

“…This leads to activation of a cellular immune response, which was exemplified in previous studies showing that PLGA nanoparticleencapsulated antigens, with or without adjuvant, may induce strong T helper type 1 and cytotoxic T cell immune response (Th1/CTL) response when delivered systemically or subcutaneously [15,17,36]. However, relatively little is known about the immune responses elicited by nanoparticle vaccines when administered intradermally using microneedles.…”

Human Plasmacytoid Dendritic Cells Phagocytose, Process, and Present Exogenous Particulate Antigen

“…This is presumably caused by controlled release of encapsulated Ag from the PLGA particle resulting in prolonged and more efficient Ag presentation compared with soluble Ag (21,37). Furthermore, ex vivo Ag loading of moDCs using microparticles is also more efficient than external loading of peptides in MHC molecules.…”

“…On the contrary, other studies show that pDCs can be activated by extracellular bacteria (S. aureus and Streptococcus pyogenes), but it was not established whether this was due to uptake of entire bacteria or mere bacterial components (8,9). Furthermore, most vaccines, such as live attenuated or inactivated pathogen-based formulations, lipid emulsions, biocompatible and biodegradable nano-and microparticles, immunostimulatory complexes, virosomes, and virus-like particles, are particulate in nature and favor delivery of antigenic cargo and/or immunostimulatory molecules to phagocytic APCs, such as myeloid and monocyte-derived DCs (moDCs) (20)(21)(22)(23). Until now, it is not known whether pDCs can play a direct role in the immune response to such particulate vaccines.…”

Biodegradable Polyelectrolyte Microcapsules: Antigen Delivery Tools with Th17 Skewing Activity after Pulmonary Delivery

“…Besides activating the innate immune system, adjuvants ideally also enhance Ag uptake and presentation by professional APCs (17). Particulate Ag delivery systems such as polymeric microspheres and liposomes have been reported to generate improved immune responses largely by such mechanism (18)(19)(20). In this paper, we have analyzed the adjuvant characteristics of polyelectrolyte microcapsules (PEMs) consisting of two dextransulfate/poly-L-arginine bilayers.…”